ASEPTIC-MENINGITIS ASSOCIATED WITH HIGH-DOSE INTRAVENOUS IMMUNOGLOBULIN THERAPY - FREQUENCY AND RISK-FACTORS

Objective: Intravenous immunoglobulin is widely used to treat various autoimmune disorders. After observing instances of aseptic meningitis in treated patients, we studied the frequency and associated risk fact ors for aseptic meningitis in patients treated with high-dose intraven ous immunoglobulin. Design: Retrospective analysis of a prospective co hort study. Setting: Tertiary research referral center. Patients: 54 c onsecutive patients with various immune-related neuromuscular diseases participating in ongoing therapeutic trials of high-dose (2 g/kg) int ravenous immunoglobulin. Measurements: Analysis of patient records for evidence of aseptic meningitis, associated risk factors, penetration of serum IgG into the cerebrospinal fluid, and clearance of cerebrospi nal fluid IgG. Results: Of 54 patients, 6 (11%; 95% CI, 4% to 23%) dev eloped aseptic meningitis within 24 hours after completion of the infu sions. Symptoms, lasting 3 to 5 days, included severe headache, mening ismus, photophobia, and fever. Cerebrospinal fluid showed pleocytosis in 4 patients (leukocyte count as high as 1169 x 10(6)/L in one patien t), eosinophilia in 3 patients, and IgG elevation in all patients (as great as 7 times the upper limit of normal in one patient). Repeat cer ebrospinal fluid and serum studies after 24 hours showed a 46% cerebro spinal fluid IgG clearance compared with an 11% clearance of serum IgG in one patient. Cerebrospinal fluid cultures were negative. Aseptic m eningitis developed in 4 of 8 patients (50%; CI, 16% to 84%) with a hi story of migraine but in only 2 of 46 (4%; CI, 0.5% to 15%) patients w ithout such a history (P = 0.003). Aseptic meningitis recurred in pati ents who had migraine despite the use of different commercial intraven ous immunoglobulin preparations and slower rates of infusion. Conclusi on: Aseptic meningitis develops in patients receiving high-dose intrav enous immunoglobulin therapy. patients with a history of migraine are more likely to develop aseptic meningitis while receiving intravenous immunoglobulin therapy, regardless of the type of commercial preparati on or the infusion rate. Possible inciting factors include the IgG its elf, various stabilizing products within each of the preparations, cyt okine release triggered by the therapy, or cerebrovascular sensitivity in migraineurs.